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This work identified a class of cyanomethylquinolones (CQs) and their carboxyl analogues as potential multitargeting antibacterial candidates. Most of the prepared compounds showed high antibacterial activities against most of the tested bacteria, exhibiting lower MIC values (0.125-2 µg/mL) than those of clinical norfloxacin, ciprofloxacin, and clinafloxacin. The low hemolysis, drug resistance, and cytotoxicity, as well as good predictive pharmacokinetics of active CQs and carboxyl analogues revealed their development potential. Furthermore, they could eradicate the established biofilm, facilitating bacterial exposure to these antibacterial candidates. These active compounds could induce bacterial death through multitargeting effects, including intercalating into DNA, up-regulating reactive oxygen species, damaging membranes directly, and impeding metabolism. Moreover, the highly active cyclopropyl CQ 15 exhibited more effective in vivo anti-MRSA potency than ciprofloxacin. These findings highlight the potential of CQs and their carboxyl analogues as multitargeting broad-spectrum antibacterial candidates for treating intractable bacterial infections.
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Antibacterianos , Testes de Sensibilidade Microbiana , Quinolonas , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Animais , Quinolonas/farmacologia , Quinolonas/química , Quinolonas/síntese química , Humanos , Relação Estrutura-Atividade , Biofilmes/efeitos dos fármacos , Camundongos , Hemólise/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Ciprofloxacina/farmacologia , Ciprofloxacina/química , Ciprofloxacina/análogos & derivados , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacosRESUMO
Chlorpyrifos (CPF), a widely used organophosphorus pesticide (OP) to control pests has been verified reproductive toxicity on mammalian oocytes. However, limited information exists on its correlation with the dysfunction of the intercellular communication in cumulus-oocyte complexes (COCs). Herein, our study utilized porcine COCs as models to directly address the latent impact of CPF on the communication between cumulus cells (CCs) and oocytes during in vitro maturation. The results demonstrated that CPF exposure decreased the rate of the first polar body (PB1) extrusion and blocked meiosis progression. Notably, the cumulus expansion of CPF-exposed COCs was suppressed significantly, accompanied by the down-regulated mRNA levels of cumulus expansion-related genes. Furthermore, the early apoptotic level was raised and the expression of BAX/BCL2 and cleaved caspase 3 was up-regulated in the CCs of CPF-exposed COCs (p < 0.05). Moreover, CPF exposure impaired mRNA levels of antioxidant enzyme-related genes, induced higher levels of reactive oxygen species (ROS) and reduced the levels of mitochondrial membrane potential (MMP) in CCs (p < 0.05). Additionally, the integrated optical density (IOD) rate (cumulus/oocyte) of calcein and the expression of connexin 43 (CX43) was increased in CPF treatment groups (p < 0.05). As well, CPF exposure reduced the expression levels of FSCN1, DAAM1 and MYO10, which resulted in a significant decrease in the number and fluorescence intensity of transzonal projections (TZPs). In conclusion, CPF inhibited the expansion of cumulus and caused oxidative stress and apoptosis as well as disturbed the function of gap junctions (GJs) and TZPs, which eventually resulted in the failure of oocyte maturation.
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Clorpirifos , Praguicidas , Suínos , Animais , Clorpirifos/toxicidade , Clorpirifos/metabolismo , Compostos Organofosforados/metabolismo , Praguicidas/metabolismo , Oócitos , Comunicação Celular , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , MamíferosRESUMO
RATIONALE: Hereditary hearing loss is known to exhibit a significant degree of genetic heterogeneity. Herein, we present a case report of a novel mutation in the tenascin-C (TNC) gene in Chinese patients with nonsyndromic hearing loss (NSHL). PATIENT CONCERNS: This includes a young deaf couple and their 2-year-old baby. DIAGNOSES: Based on the clinical information, hearing test, metagenomic next-generation sequencing (mNGS), Sanger sequencing, protein function and structure analysis, and model prediction, in our case, the study results revealed 2 heterozygous mutations in the TNC gene (c.2852C>T, p.Thr951Ile) and the TBC1 domain family member 24 (TBC1D24) gene (c.1570C>T, p.Arg524Trp). These mutations may be responsible for the hearing loss observed in this family. Notably, the heterozygous mutations in the TNC gene (c.2852C>T, p.Thr951Ile) have not been previously reported in the literature. INTERVENTIONS: Avoid taking drugs that can cause deafness, wearing hearing AIDS, and cochlear implants. OUTCOMES: Regular follow-up of family members is ongoing. LESSONS: The genetic diagnosis of NSHL holds significant importance as it helps in making informed treatment decisions, providing prognostic information, and offering genetic counseling for the patient's family.
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Surdez , Perda Auditiva Neurossensorial , Perda Auditiva , Tenascina , Pré-Escolar , Humanos , China , Surdez/genética , Proteínas Ativadoras de GTPase/genética , Perda Auditiva/genética , Perda Auditiva Neurossensorial/genética , Mutação , Linhagem , Tenascina/genéticaRESUMO
In photo-Fenton technology, the narrower pH range limits its practical application for antibiotic wastewater remediation. Therefore, in this study, a Z-scheme heterojunction photo-Fenton catalyst was constructed by Fe-doped graphite-phase carbon nitride in combination with bismuth molybdate for the degradation of typical antibiotics. Fe doping can shorten the band gap and increase visible-light absorption. Simultaneously, the constructed Z-scheme heterojunction provides a better charge transfer pathway for the photo-Fenton reaction. Within 30 min, Fe3CN/BMO-3 removed 95.54% of tetracycline hydrochloride (TC), and its remarkable performance was the higher Fe3+/Fe2+ conversion efficiency through the decomposition of H2O2. The Fe3CN/BMO-3 catalyst showed remarkable photo-Fenton degradation performance in a wide pH range (3.0-11.0), and it also had good stability in the treatment of TC wastewater. Furthermore, the order of action of the active species was h+ > ·O2- > 1O2 > ·OH, and the toxicity assessment suggested that Fe3CN/BMO-3 was effective in reducing the biotoxicity of TC. The catalyst proved to be an economically feasible and applicable material for antibiotic photo-Fenton degradation, and this study provides another perspective on the application of elemental doping and constructed heterojunction photo-Fenton technology for antibiotic water environmental remediation.
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Antibacterianos , Bismuto , Peróxido de Hidrogênio , Ferro , Molibdênio , Poluentes Químicos da Água , Bismuto/química , Antibacterianos/química , Antibacterianos/toxicidade , Concentração de Íons de Hidrogênio , Ferro/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade , Peróxido de Hidrogênio/química , Molibdênio/química , Catálise , Grafite/química , Grafite/toxicidade , Compostos de Nitrogênio/química , Compostos de Nitrogênio/toxicidade , Nitrilas/química , Nitrilas/toxicidade , Águas Residuárias/químicaRESUMO
Canonical correlation analysis (CCA), Multivariate synchronization index (MSI), and their extended methods have been widely used for target recognition in Brain-computer interfaces (BCIs) based on Steady State Visual Evoked Potentials (SSVEP), and covariance calculation is an important process for these algorithms. Some studies have proved that embedding time-local information into the covariance can optimize the recognition effect of the above algorithms. However, the optimization effect can only be observed from the recognition results and the improvement principle of time-local information cannot be explained. Therefore, we propose a time-local weighted transformation (TT) recognition framework that directly embeds the time-local information into the electroencephalography signal through weighted transformation. The influence mechanism of time-local information on the SSVEP signal can then be observed in the frequency domain. Low-frequency noise is suppressed on the premise of sacrificing part of the SSVEP fundamental frequency energy, the harmonic energy of SSVEP is enhanced at the cost of introducing a small amount of high-frequency noise. The experimental results show that the TT recognition framework can significantly improve the recognition ability of the algorithms and the separability of extracted features. Its enhancement effect is significantly better than the traditional time-local covariance extraction method, which has enormous application potential.
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Interfaces Cérebro-Computador , Humanos , Potenciais Evocados Visuais , Reconhecimento Automatizado de Padrão/métodos , Reconhecimento Psicológico , Eletroencefalografia/métodos , Algoritmos , Estimulação LuminosaRESUMO
Unique benzopyridone cyanoacetates (BCs) as new type of promising broad-spectrum antibacterial candidates were discovered with large potential to combat the lethal multidrug-resistant bacterial infections. Many prepared BCs showed broad antibacterial spectrum with low MIC values against the tested strains. Some highly active BCs exhibited rapid sterilization capacity, low resistant trend and good predictive pharmacokinetic properties. Furthermore, the highly active sodium BCs (NaBCs) displayed low hemolysis and cytotoxicity, and especially octyl NaBC 5g also showed in vivo potent anti-infective potential and appreciable pharmacokinetic profiles. A series of preliminary mechanistic explorations indicated that these active BCs could effectively eliminate bacterial biofilm and destroy membrane integrity, thus resulting in the leakage of bacterial cytoplasm. Moreover, their unique structures might further bind to intracellular DNA, DNA gyrase and topoisomerase IV through various direct noncovalent interactions to hinder bacterial reproduction. Meanwhile, the active BCs also induced bacterial oxidative stress and metabolic disturbance, thereby accelerating bacterial apoptosis. These results provided a bright hope for benzopyridone cyanoacetates as potential novel multitargeting broad-spectrum antibacterial candidates to conquer drug resistance.
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Antibacterianos , Inibidores da Topoisomerase II , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias , DNA Girase/metabolismo , DNA Topoisomerase IV , Testes de Sensibilidade Microbiana , Inibidores da Topoisomerase II/farmacologia , Piridonas/química , Piridonas/farmacologia , Nitrilas/química , Nitrilas/farmacologiaRESUMO
A new type of benzopyrone-mediated quinolones (BMQs) was rationally designed and efficiently synthesized as novel potential antibacterial molecules to overcome the global increasingly serious drug resistance. Some synthesized BMQs effectively suppressed the growth of the tested strains, outperforming clinical drugs. Notably, ethylidene-derived BMQ 17a exhibited superior antibacterial potential with low MICs of 0.5-2 µg/mL to clinical drugs norfloxacin, it not only displayed rapid bactericidal performance and inhibited bacterial biofilm formation, but also showed low toxicity toward human red blood cells and normal MDA-kb2 cells. Mechanistic investigation demonstrated that BMQ 17a could effectually induce bacterial metabolic disorders and promote the enhancement of reactive oxygen species to disrupt the bacterial antioxidant defense system. It was found that the active molecule BMQ 17a could not only form supramolecular complex with lactate dehydrogenase, which disturbed the biological functions, but also effectively embed into calf thymus DNA, thus affecting the normal function of DNA and achieving cell death. This work would provide an insight into developing new molecules to reduce drug resistance and expand antibacterial spectrum.
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Antibacterianos , Quinolonas , Humanos , Antibacterianos/farmacologia , DNA Girase/metabolismo , Testes de Sensibilidade Microbiana , Norfloxacino/farmacologia , Quinolonas/farmacologia , Quinolonas/metabolismo , Benzopiranos/metabolismo , Benzopiranos/farmacologiaRESUMO
BACKGROUND: Immune cell heterogenicity is known to determine the therapeutic response to cancer progression. Neoadjuvant chemoimmunotherapy (NACI) has shown clinical benefits in some patients with advanced head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism behind this clinical response is unknown. The efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting NACI response in advanced HNSCC. METHODS: We performed combined single-cell RNA sequencing (scRNA-seq) and multiplex immunofluorescence (mIHC) staining with tumor samples derived from NACI-treated HNSCC patients to identify a new tumor-infiltrating cell (TIL) subtype, CD103+ CD8+ TILs, associated with clinical response, while both in vitro and in vivo assays were carried out to determine its antitumor efficiency. The regulatory mechanism of the CD103+ CD8+ TILs population was examined by performing cell-cell interaction analysis of the scRNA-seq data and spatial analysis of the mIHC images. RESULTS: We established intratumoral CD103+ CD8+ TILs density as a determinant of NACI efficacy in cancers. Our scRNA-seq results indicated that the population of CD103+ CD8+ TILs was dramatically increased in the responders of NACI-treated HNSCC patients, while mIHC analysis confirmed the correlation between intratumoral CD103+ CD8+ TILs density and NACI efficacy in HNSCC patients. Further receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to NACI. Functional assays showed that CD103+ CD8+ TILs were tumor-reactive T cells, while programmed cell death protein-1 (PD-1) blockade enhanced CD103+ CD8+ TILs cytotoxicity against tumor growth in vivo. Mechanistically, targeting the triggering receptor expressed on myeloid cells 2-positive (TREM2+ ) macrophages might enhance the population of CD103+ CD8+ TILs and facilitate antitumor immunity during NACI treatment. CONCLUSIONS: Our study highlights the impact of intratumoral CD103+ CD8+ TILs density on NACI efficacy in different cancers, while the efforts to elevate its population warrant further clinical investigation.
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Linfócitos T CD8-Positivos , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Linfócitos T CD8-Positivos/metabolismo , Terapia Neoadjuvante , Neoplasias de Cabeça e Pescoço/tratamento farmacológicoRESUMO
Background and Purpose: The main goal of hospice care is to improve the quality of life for people who are at the end-of-life phase. However, investigations on the awareness of hospice care among community-dwelling elderly participants are limited. This work aimed to reveal the awareness status of hospice care and explore the factors influencing the awareness rate among elderly participants. Methods: A questionnaire survey was conducted among individuals aged 60 years and above. Results: A total of 4,969 individuals aged 60 years and above were randomly selected from 48 primary medical institutions in Handan. The awareness rate of hospice care in the baseline survey was 19.3% (n = 959). All included individuals were divided into two groups in accordance with their awareness of hospice care. The awareness of hospice care among participants with low educational level, living alone, and afraid of talking about death was low (p < .05). Implications for Practice: The level of awareness of hospice care among community-dwelling elderly participants is low. The influencing factors included educational level, living status, and fear of talking about death. The community-dwelling elderly participants' awareness of hospice care must be improved. It is recommended that public medical education and training should be enhanced to improve knowledge and awareness of hospice care among community-dwelling elderly residents with low educational level, living alone, and afraid of talking about death.
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Cuidados Paliativos na Terminalidade da Vida , Idoso , Humanos , Escolaridade , Medo , Vida Independente , Qualidade de Vida , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Circular RNAs (circRNAs), with their multilevel and versatile regulation, have emerged as promising targets for treating complex and heterogeneous malignancies such as oral squamous cell carcinoma (OSCC). It is crucial to explore the function of key circRNAs and elucidate the underlying mechanisms to establish an effective in vivo delivery system to better utilize circRNAs as cancer treatment strategies. MATERIALS AND METHODS: circRNA (circ-OCAC) was identified as significantly downregulated in tumor samples compared to paracancerous tissues by RNA-seq analysis of eight pairs of OSCC tissues. Functional experiments of circ-OCAC were performed both in vitro and in vivo. The interactions between circ-OCAC and miR-411-5p were clarified by RNA pull down and RNA immunoprecipitation (RIP) assays. RESULTS: We observed that circ-OCAC inhibits OSCC growth and metastasis by blocking the PI3K/Akt signaling pathway. To translate this observation in vivo, a pH-responsive nanoparticle (pNP) was developed to target circ-OCAC. Our results confirmed the advantages of the pNP-circ-OCAC system: high tumor enrichment capacity and good biosafety, which resulted in a significantly enhanced antitumor effect. CONCLUSIONS: This study demonstrated that targeting circ-OCAC serves as a promising potential therapeutic strategy for OSCC.
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Introduction: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae pose a huge threat to human health, especially in the context of complicated urinary tract infections (cUTIs). Carbapenems and piperacillin-tazobactam (PTZ) are two antimicrobial agents commonly used to treat cUTIs. Methods: A monocentric retrospective cohort study focused on the treatment of cUTIs in adults was conducted from January 2019 to November 2021. Patients with a positive urine culture strain yielding ≥ 103 colony-forming units per milliliter (CFU/mL), and sensitive to PTZ and carbapenems, were included. The primary endpoint was clinical success after antibiotic therapy. The secondary endpoint included rehospitalization and 90-day recurrence of cUTIs caused by ESBL-producing Enterobacteriaceae. Results: Of the 195 patients included in this study, 110 were treated with PTZ while 85 were administered meropenem. The rate of clinical cure was similar between the PTZ and meropenem groups (80% vs. 78.8%, p = 0.84). However, the PTZ group had a lower duration of total antibiotic use (6 vs. 9; p < 0.01), lower duration of effective antibiotic therapy (6 vs. 8; p < 0.01), and lower duration of hospitalization (16 vs. 22; p < 0.01). Discussion: In terms of adverse events, the safety of PTZ was higher than that of meropenem in the treatment of cUTIs.
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Infecções por Enterobacteriaceae , Pielonefrite , Infecções Urinárias , Adulto , Humanos , Meropeném/uso terapêutico , Piperacilina/efeitos adversos , Estudos Retrospectivos , Inibidores de beta-Lactamases/uso terapêutico , Ácido Penicilânico/efeitos adversos , Antibacterianos/efeitos adversos , Combinação Piperacilina e Tazobactam/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Pielonefrite/tratamento farmacológico , Enterobacteriaceae , Carbapenêmicos/uso terapêutico , beta-Lactamases/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológicoRESUMO
The electron-rich five-membered aromatic aza-heterocyclic imidazole, which contains two nitrogen atoms, is an important functional fragment widely present in a large number of biomolecules and medicinal drugs; its unique structure is beneficial to easily bind with various inorganic or organic ions and molecules through noncovalent interactions to form a variety of supramolecular complexes with broad medicinal potential, which is being paid an increasing amount of attention regarding more and more contributions to imidazole-based supramolecular complexes for possible medicinal application. This work gives systematical and comprehensive insights into medicinal research on imidazole-based supramolecular complexes, including anticancer, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, and anti-inflammatory aspects as well as ion receptors, imaging agents, and pathologic probes. The new trend of the foreseeable research in the near future toward imidazole-based supramolecular medicinal chemistry is also prospected. It is hoped that this work provides beneficial help for the rational design of imidazole-based drug molecules and supramolecular medicinal agents and more effective diagnostic agents and pathological probes.
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Pelophylax nigromaculatus is a common commercial specie of frogs that generally cultured throughout China. With the application of high-density culture, P. nigromaculatus can be co-infected by two or more pathogens, which thereby induce synergistic influence on the virulence of the infection. In this study, two bacterial strains were simultaneously isolated from diseased frogs by incubating on Luria-Bertani (LB) agar. Isolates were identified as Klebsiella pneumoniae and Elizabethkingia miricola by morphological, physiological and biochemical features, as well as 16S rRNA sequencing and phylogenetic analysis. The whole genome of K. pneumoniae and E. miricola isolates consist single circular chromosome of 5,419,557 bp and 4,215,349 bp, respectively. The genomic sequence analysis further indicated that K. pneumoniae isolate conserved 172 virulent and 349 antibiotic-resistance genes, whereas E. miricola contained 24 virulent and 168 antibiotic resistance genes. In LB broth, both isolates could grow well at 0%-1% NaCl concentration and pH 5-7. Antibiotic susceptibility testing revealed that both K. pneumoniae and E. miricola were resistant to kanamycin, neomycin, ampicillin, piperacillin, carbenicillin, enrofloxacin, norfloxacin and sulfisoxazole. Histopathological studies showed that co-infection caused considerable lesions in the tissues of brain, eye, muscle, spleen, kidney and liver, including cell degeneration, necrosis, hemorrhage and inflammatory cell infiltration. The LD50 of K. pneumoniae and E. miricola isolates were 6.31 × 105 CFU/g and 3.98 × 105 CFU/g frog weight, respectively. Moreover, experimentally infected frogs exhibited quick and higher mortality under coinfection with K. pneumoniae and E. miricola than those single challenge of each bacterium. To date, no natural co-infection by these two bacteria has been reported from frogs and even amphibians. The results will not only shed light on the feature and pathogenesis of K. pneumoniae and E. miricola, but also highlight that co-infection of these two pathogen is a potential threat to black-spotted frog farming.
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Coinfecção , Infecções por Klebsiella , Animais , Klebsiella pneumoniae , Coinfecção/veterinária , Filogenia , RNA Ribossômico 16S/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ranidae/microbiologia , Infecções por Klebsiella/microbiologiaRESUMO
The successful use of exosomes in therapy after myocardial infarction depends on an improved understanding of their role in cardiac signaling and regulation. Here, we report that exosomes circulating after myocardial infarction (MI) carry LncRNA TUG1 which downregulates angiogenesis by disablement of the HIF-1α/VEGF-α axis and that this effect can be counterbalanced by remote ischemic conditioning (RIC). Rats with MI induced through left coronary artery ligation without (MI model) and with reperfusion (ischemia/reperfusion I/R model) were randomized to RIC, or MI (I/R) or sham-operated (SO) control. Data from one cohort study and one randomized-controlled trial of humans with MI were also utilized, the former involving patients who had not received percutaneous coronary intervention (PCI) and the latter patients with PCI. Exosome concentrations did not differ between intervention groups (RIC vs. control) in rats (MI and I/R model) as well as humans (with and without PCI). However, MI and I/R exosomes attenuated HIF-1α, VEGF-α, and endothelial function. LncRNA TUG1 was increased in MI and I/R exosomes, but decreased in SO and RIC exosomes. HIF-1α expression was downregulated with MI and I/R exosomes but increased with RIC exosomes. Exosome inhibition suppressed HIF-1α upregulation through RIC exosomes. VEGF-α was identified as HIF-1α-regulated target gene. Knockdown of HIF-1α decreased VEGF-α, endothelial cell capability, and tube formation. Overexpression of HIF-1α exerted opposite effects. Transfection and co-transfection of 293 T cells with exosome-inhibitor GW4869 and HIF-1α inhibitor si-HIF-1α confirmed the exosomal-LncRNA TUG1/HIF-1α/VEGF-α pathway. LncRNA TUG1 is a potential therapeutic target after MI with or without reperfusion through PCI.
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Infarto do Miocárdio , Intervenção Coronária Percutânea , RNA Longo não Codificante , Humanos , Ratos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Estudos de Coortes , Fator A de Crescimento do Endotélio Vascular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genéticaRESUMO
BACKGROUND: Acetyl-coenzyme A carboxylase 1 (ACC1) regulates lipid homeostasis, T helper (Th) cell differentiation, oxidative stress, inflammation response, and neurological process, engaging in acute ischemic stroke (AIS) pathogenesis, while its clinical utility in AIS is unclear. Hence, this study intended to explore the correlation among blood ACC1, Th17, and Th1 cells, and ACC1's potency as a prognostic biomarker for AIS management. METHODS: ACC1 in peripheral blood mononuclear cells (PBMCs) of 160 AIS patients and 30 controls were determined using RT-qPCR; blood Th17 and Th1 cells in AIS patients were quantified by flow cytometry. RESULTS: ACC1 was increased in AIS patients compared with controls (median (interquartile range): 2.540 (1.753-3.548) vs. 0.980 (0.655-1.743), p < 0.001), which exhibited a good value to reflect AIS risk with the area under the curve of 0.872 (95% CI: 0.805-0.939). Moreover, ACC1 was positively linked with Th17 (r = 0.374, p < 0.001) and Th1 (r = 0.178, p = 0.024) cells in AIS patients. Additionally, ACC1 (r = 0.328, p < 0.001), Th17 (r = 0.272, p = 0.001), and Th1 cells (r = 0.195, p = 0.014) were positively associated with the National Institutes of Health Stroke Scale score in AIS patients. ACC1 high vs. low (p = 0.038) and Th17 high vs. low (p = 0.026) were related to shortened recurrence-free survival (RFS) in AIS patients, while Th1 cells (p = 0.179) were not correlated with RFS. Whereas ACC1 (p = 0.248), Th17 (p = 0.079), and Th1 cells (p = 0.130) were not linked with overall survival (OS) in AIS patients. CONCLUSION: Circulating ACC1 overexpression correlates with increased Th17, Th1 cells, NIHSS score, and shortened RFS in AIS patients.
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AVC Isquêmico , Acidente Vascular Cerebral , Acetil-CoA Carboxilase , Biomarcadores , Coenzima A , Humanos , Leucócitos Mononucleares , Lipídeos , Prognóstico , Células Th1 , Células Th17RESUMO
Caregiver education program has been applied to stroke patients, while its effect on mental health in stroke patients is still obscure. This study aimed to assess the impact of the WeChat-based caregiver education (WBCE) program on cognition, anxiety, and depression in stroke patients. Totally, 170 patients with ischemic stroke were included. They were randomized at a 1:1 ratio to the WBCE group (N = 86) and control care (CC) group (N = 84), and their caregivers received WBCE or CC for 12 months, respectively. Mini-mental state examination (MMSE) score was increased in the WBCE group compared with that in the CC group at the 9th month (M9) (27.2 ± 1.9 vs 26.6 ± 1.6, P = 0.017) and M12 (27.1 ± 1.8 vs 26.5 ± 1.5, P = 0.015), while cognitive impairment rate was decreased in WBCE group compared with that in CC group at 12th month (M12) (30.2% vs 45.2%, P=0.043). In the meantime, the Hospital Anxiety and Depression Scale (HADS) for Anxiety score (6.5 ± 3.1 vs 7.5 ± 2.8, P = 0.020), HADS for depression score (6.7 ± 3.1 vs 7.7 ± 3.3, P = 0.040) and depression rate (33.7% vs 48.8%, P = 0.046) in WBCE group were reduced compared with those in CC group at M12. Besides, an elevation in the satisfaction score of patients at M12 (8.0 ± 1.2 vs 7.4 ± 1.2, P = 0.002) and that of caregivers at 6th months (M6) (6.6 ± 1.1 vs 6.2 ± 1.3, P = 0.038) and M12 (7.2 ± 1.1 vs 6.8 ± 1.4, P=0.042) were found in WBCE group compared with CC group. WBCE program not only improves the satisfaction of stroke patients and caregivers but also attenuates cognitive impairment and depression in stroke patients.
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Disfunção Cognitiva , Acidente Vascular Cerebral , Ansiedade/etiologia , Ansiedade/psicologia , Ansiedade/terapia , Cuidadores , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/terapia , Depressão/etiologia , Depressão/psicologia , Depressão/terapia , Humanos , Satisfação do Paciente , Satisfação Pessoal , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologiaRESUMO
In the present work, a novel Ti-Al-C-Nb composite was prepared using in situ selective laser forming (ISLF). The formation mechanism of the Ti-Al-C-Nb bulks, which were synthesized using elemental titanium, aluminum, and carbon (graphite) powders via ISLF techniques, was investigated. The results showed that the Ti3Al and TiC phases were the dominant synthesis products during the chemical reactions, and these occurred during the ISLF process. The size of the fine nanoscale crystal TiC grains could reach 157 nm at an energy level of 60 J/mm3. The porous structure of the ISLF specimens was disclosed, and an open porosity of 20-44% was determined via the scanning speed and the laser power. Both the high dynamic viscosity and the reactions of the raw powders led to the generation of a considerable number of pores, whereas the specimen processed using 45 W and 100 mm/s possessed the lowest degree of open porosity.
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The P300-based brain-computer interfaces (BCIs) enable participants to communicate by decoding the electroencephalography (EEG) signal. Different regions of the brain correspond to various mental activities. Therefore, removing weak task-relevant and noisy channels through channel selection is necessary when decoding a specific type of activity from EEG. It can improve the recognition accuracy and reduce the training time of the subsequent models. This study proposes a novel block sparse Bayesian-based channel selection method for the P300 speller. In this method, we introduce block sparse Bayesian learning (BSBL) into the channel selection of P300 BCI for the first time and propose a regional smoothing BSBL (RSBSBL) by combining the spatial distribution properties of EEG. The RSBSBL can determine the number of channels adaptively. To ensure practicality, we design an automatic selection iteration strategy model to reduce the time cost caused by the inverse operation of the large-size matrix. We verified the proposed method on two public P300 datasets and on our collected datasets. The experimental results show that the proposed method can remove the inferior channels and work with the classifier to obtain high-classification accuracy. Hence, RSBSBL has tremendous potential for channel selection in P300 tasks.
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It is difficult to identify optimal cut-off frequencies for filters used with the common spatial pattern (CSP) method in motor imagery (MI)-based brain-computer interfaces (BCIs). Most current studies choose filter cut-frequencies based on experience or intuition, resulting in sub-optimal use of MI-related spectral information in the electroencephalography (EEG). To improve information utilization, we propose a SincNet-based hybrid neural network (SHNN) for MI-based BCIs. First, raw EEG is segmented into different time windows and mapped into the CSP feature space. Then, SincNets are used as filter bank band-pass filters to automatically filter the data. Next, we used squeeze-and-excitation modules to learn a sparse representation of the filtered data. The resulting sparse data were fed into convolutional neural networks to learn deep feature representations. Finally, these deep features were fed into a gated recurrent unit module to seek sequential relations, and a fully connected layer was used for classification. We used the BCI competition IV datasets 2a and 2b to verify the effectiveness of our SHNN method. The mean classification accuracies (kappa values) of our SHNN method are 0.7426 (0.6648) on dataset 2a and 0.8349 (0.6697) on dataset 2b, respectively. The statistical test results demonstrate that our SHNN can significantly outperform other state-of-the-art methods on these datasets.
Assuntos
Interfaces Cérebro-Computador , Imaginação , Algoritmos , Eletroencefalografia/métodos , Humanos , Redes Neurais de Computação , Processamento de Sinais Assistido por ComputadorRESUMO
Human milk N-glycome promotes the growth of Bifidobacterium longum subsp. infantis ATCC 15697. However, the action mode of, and the major functional components for, the bifidogenic function of human milk N-glycome remain unclear. In this study, we demonstrated that milk N-glycome was transferred in an intact form from culture into the bacterial cell and then decomposed intracellularly, evidenced by the following facts: (1) No UHPLC peak shift of N-glycome recovered from culture was observed. (2) No milk N-glycan specific monosugar was detected in culture supernatant. (3) High intracellular exoglycosidase activities were detected. (4) Fluorescently labeled N-glycans were found to be located intracellularly using Laser Scanning Confocal Microscopy (LSCM). Regarding the principal components identification, a novel sequential deglycosylation-based strategy was established. Degalactosylation, defucosylation-desialylation, and defucosylation-desialylation-degalactosylation treatments of human milk N-glycome showed that galactose-containing glycans were the principal components for the probiotic function of human milk N-glycome towards B. infantis ATCC 15697.